A Multicenter, International, Randomized, Double-blind, Placebo-controlled Clinical Trial of the Aldosterone Synthase Inhibitor BI 690517 in Combination With Empagliflozin in Patients With Chronic Kidney Disease
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 11,000
- 试验地点
- 859
- 主要终点
- Time to first occurrence of the primary composite outcome of: (i) Kidney disease progression*; or (ii) Hospitalization for heart failure; or (iii) Cardiovascular death.
研究概览
简要总结
This study is open to adults with chronic kidney disease at risk of progression. People with and without type 2 diabetes can take part in this study. The study is open to people who take other medicines called angiotensin converting enzyme inhibitors (ACEi) or angiotensin receptor blockers (ARB). People who already take empagliflozin or any other sodium-glucose cotransporter-2 inhibitor (SGLT2i) can also join. The study is also open to people who currently do not take any of these treatments. The purpose of this study is to find out whether a medicine called BI 690517 helps people with chronic kidney disease when taken in combination with a study medicine called empagliflozin. Worsening of kidney function increases the risk for kidney failure, cardiovascular disease, and heart failure hospitalisation.
After a run-in period, during which participants are confirmed to be receiving clinically appropriate renin-angiotensin system blockade and are established on empagliflozin, they are randomly assigned (by chance) to 1 of 2 groups. One group receives BI 690517 tablets, and the other group receives placebo tablets. Placebo tablets look like BI 690517 but do not contain any medicine. Participants take 1 study tablet once a day, in addition to empagliflozin, for the duration of the study.
The doctors document when participants experience worsening of their kidney disease, go to hospital due to heart failure, or die of cardiovascular problems during the study. The time to these events is compared between the 2 treatment groups to see whether the treatment works. The study continues until the required number of events have occurred which is about 3 to 4 years. During this time, participants visit the study site about 5 times within the first 6 months. Then they visit the study site every 6 months. At the visits, doctors regularly check participants' health, take blood and urine samples, measure blood pressure and weight, check kidney function, and take note of any unwanted effects.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Evidence of chronic kidney disease (CKD) at risk of kidney disease progression is defined on the basis of local laboratory results recorded at least 3 months before and at the time of the Screening visit, and requires:
- •Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) eGFR ≥20 <45 mL/min/1.73m² (irrespective of diabetes status); or
- •No self-reported diabetes: CKD-EPI eGFR ≥45 <90 mL/min/1.73m² with urine albumin-to-creatinine ratio (uACR) ≥150 mg/g (or protein-to-creatinine ratio ≥225 mg/g); or
- •Self-reported diabetes: CKD-EPI eGFR ≥45 <90 mL/min/1.73m² with uACR ≥30 mg/g (or protein-to-creatinine ratio ≥45 mg/g).
- •Neither requires an Aldosterone Synthase inhibitor (ASi) or Mineralocorticoid Receptor Antagonist (MRA), nor that such treatment is definitely inappropriate.
排除标准
- •Blood potassium of >5.2 mmol/L at screening visit
- •Blood Alanine Transaminase (ALT) or Aspartate Transaminase (AST) >3x Upper Limit of Normal (ULN) at Screening visit (only one is required, with ALT preferred)
- •Known liver cirrhosis
- •On dialysis, functioning kidney transplant, or scheduled living donor transplant
- •Treated with new immunosuppression therapy for new (or relapse/flare of pre-existing) kidney disease within the last 60 days
- •Receiving more than one Renin-Angiotensin System (RAS) inhibitor (i.e. on dual therapy with two of an Angiotensin-Converting Enzyme inhibitor (ACEi), Angiotensin Receptor Blocker (ARB) or direct renin inhibitor)
- •Currently treated with an Mineralocorticoid Receptor Antagonist (MRA) (e.g. spironolactone, eplerenone, finerenone)
- •Currently treated with systemic mineralocorticoid replacement therapy (e.g. fludrocortisone) Further exclusion criteria apply.
研究组 & 干预措施
Part 2: Randomized treatment, follow-up period, treatment group
干预措施: BI 690517 (Drug)
Part 2: Follow-up period, placebo group
干预措施: Placebo matching BI 690517 (Drug)
Part 2: Follow-up period, placebo group
干预措施: Empagliflozin (Drug)
Part 1: Run-in period (all participants)
- Participant will receive empagliflozin (called Type E) together with study tablets (called Type F) prior to later randomisation to the main study treatment (Type M).
- This run-in period allows empagliflozin to be established and have its effects on kidney function before randomisation, and to make sure participant can tolerate empagliflozin long-term. Participants will not routinely know whether type F treatment is active or inactive so that participants can become familiar with taking main study tablet (Type M) after randomization.
干预措施: Empagliflozin (Drug)
Part 2: Randomized treatment, follow-up period, treatment group
干预措施: Empagliflozin (Drug)
结局指标
主要结局
Time to first occurrence of the primary composite outcome of: (i) Kidney disease progression*; or (ii) Hospitalization for heart failure; or (iii) Cardiovascular death.
时间窗: up to 4 years
Kidney disease progression is defined as kidney failure or a sustained decline of ≥40% in estimated Glomerular Filtration Rate (eGFR) from randomization
次要结局
- Time to first event of kidney failure, hospitalization for heart failure or cardiovascular death(up to 4 years)
- Occurrences of hospitalizations for heart failure (first and any subsequent, combined) or cardiovascular death(up to 4 years)
- Occurrences of hospitalizations from any cause (first and any subsequent, combined)(up to 4 years)
- Time to first event of kidney disease progression or cardiovascular death(up to 4 years)
- Time to death from any cause(up to 4 years)
- Key secondary outcome: Annual rate of change in eGFR from 3 month visit until last scheduled visit (i.e. chronic eGFR slope)(up to 4 years)
- Time to kidney disease progression(up to 4 years)
- Key secondary outcome: Time to first event of kidney failure, hospitalization for heart failure or cardiovascular death(up to 4 years)
- Key secondary outcome: Time to first event of hospitalization for heart failure or cardiovascular death(up to 4 years)
- Key secondary outcome: Occurrences of hospitalizations from any cause (first and any subsequent, combined) or death from any cause(up to 4 years)
- Key secondary outcome: Time to death from any cause(up to 4 years)
- Key secondary outcome: Annual rate of change in eGFR from 1 month until last scheduled visit (i.e. chronic eGFR slope)(up to 4 years)